tPA (Tissue Plasminogen Activator) converts thrombus-bound plasminogen to plasmin, which degrades cross-linked fibrin. tPA is used clinically in the emergency treatment of ischemic stroke, but its use can lead to major complications, including hemorrhagic transformation and neurotoxicity. Furthermore, the tPA must be administered within a short treatment time window of about 2-3 hours after the ischemic event.
Human Annexin A2 is a cell surface receptor for both plasminogen and tPA, and forms a recombinant human Annexin A2 (rA2)-tPA-plasminogen triple complex. Co-administration of Annexin A2 lowers the effective concentration of tPA required to convert plasminogen to plasmin, reduces the risk of neurotoxic and hemorrhagic complications, and prolongs the treatment window. See, e.g., Zhu et al, J. Cereb. Blood Flow Metab. 30:1137-1146 (2010) and US2011/129526.